Evaluation of Ampicillin and Ceftriaxone on Ethanol Consumption as Compared to Naltrexone in Alcohol Dependant Rats

Context: Extracellular glutamate level in reward centre of brain increases during ethanol drinking sessions. Hence, it can be hypothesized that drugs which decrease extracellular glutamate might have deaddictive properties. It has been shown that β-lactam antibiotics are potent stimulators of glutamate transporter 1(GLT1) expression. Previous studies have shown that ceftriaxone decreases ethanol consumption but this has not been compared to standard line of treatment (naltrexone). Also, no study was conducted for testing ampicillin even if in an in-vitro experiment ampicillin has shown to increase GLT1 levels more than ceftriaxone. Hence, our study’s objectives were to compare efficacy of ceftriaxone and ampicillin with naltrexone on ethanol consumption in rats.
Methods: Permission of ethics committee was taken. Study was divided into two parts. Part I included standardization of model & Part II included 8 groups of six rats each. Group 1: vehicle control, Group 2: 1mg/kg/d naltrexone, Group 3: 100mg/kg/d ceftriaxone, Group 4: 200mg/kg/d ceftriaxone, Group 5: 100mg/kg/d ampicillin, Group 6: 200mg/kg/d ampicillin were given i.p injections for 15 days and Group 7: 200mg/kg ceftriaxone & Group 8: 200mg/kg ampicillin i.p. single dose. Parameters measured were ethanol & water intake per day for 15 days.
Results: Groups 2 to 8 showed statistically significant decrease in ethanol intake as compared to vehicle control. Also, group 3 & 4 showed an increase in water consumption as compared to Group 1.
Conclusions: Our study recommends that drugs acting on glutamate pathways like ceftriaxone and ampicillin can be explored for treatment of alcohol dependence.